Method for using a carbamoyl fluoride as fluorinating agent

ABSTRACT

The invention concerns a method for using a carbamoyl fluoride as fluorinating agent. Said method consists in treating a derivative bearing a halogen-containing carbon, with a carbamoyl fluoride at a temperature not less than 70 ° C. and in maintaining the ratio between the sum of hydrofluoric acid (HF) and carbamoyl fluoride as well as between the sum of exchangeable halogen atoms, isocyanate functions and carbamoyl fluoride [(HF+carbamoyl fluoride)/(exchangeable halogen+isocyanate+carbamoyl fluoride)] at a value not more than 1.2; then in carrying out a catalysis process with tin, antimony and/or titanium salt. The invention is applicable to synthesis of fluorinated derivatives.

This application is an application under 35 U.S.C. Section 371 ofInternational Application Number PCT/FR02/00075 filed on Jan. 10, 2002.

A subject matter of the present invention is a process for the synthesisof fluorinated compounds using, as fluorine source, the carbamoylfluoride which is in equilibrium with the isocyanate and thehydrofluoric acid.

The present invention is targeted more particularly at the synthesis ofcompounds simultaneously exhibiting a perfluorinated carbon, or in anycase a perhalogenated carbon, and an isocyanate functional group, inparticular an isocyanate functional group deriving from an anilinefunctional group.

The perhalogenated carbon, generally a perfluorinated carbon, is acarbon of aliphatic nature, that is to say that it has sp³hybridization.

The term “perhalogenated carbon” should be understood as meaning acarbon of sp³ nature which does not carry hydrogen and which comprises,in addition to its bond with the part of the molecule carrying theisocyanate functional group, at most 2 radicals, advantageously at most1 radical, all the other atoms being halogens; said radicals areadvantageously chosen from electron-withdrawing groups, this being thecase in particular when there are 2 of them. Although not perhalogenatedstricto sensu, carbons carrying two halogens and one hydrogen arecapable of being treated like the perhalogenated compounds in the strictsense. However, they are more sluggish. Carbons carrying exchangeable orexchanged halogens are also denoted by the term “halophoric carbon(s)”.

During recent decades, and more specifically during the last decade,compounds carrying a perhalogenated and in particular perfluorinatedaliphatic atom have become increasingly important in the field ofagrochemistry and of pharmaceuticals. This is because theseperfluorinated products, generally comprising a perfluoromethyl orperfluoroethyl radical, have physiological properties which render themolecules of which they are composed particularly active.

Consequently, numerous proposals for processes resulting in saidproducts have blossomed. Generally, the fluorinating agent is liquidhydrofluoric acid, while the intermediate substrate or the startingsubstrate are isocyanates.

Mention may thus be made, in the case of anilines carryingtrifluoromethyl groups, of the Occidental Chemical Corporation patentNo. EP-A-129 214 and the patent of the predecessor in law of theApplicant Company, namely the European patent filed on behalf ofRhône-Poulenc Spécialités Chimiques and granted under the numberEP-B-152 310.

More recently, a European patent on behalf of Hoechst A. G. waspublished under the number EP-A-639 556.

These documents describe various alternative treatment forms by thehydrofluoric acid route and are often a good means of appreciating thelimitations of this route.

According to this technique, the starting point is the protection of theamine functional group by an isocyanate functional group, for example byphosgenation. The carbon which will have to be in a perfluorinated formin the final stage is then chlorinated, generally by the free radicalroute. Finally, the chlorinated compound thus obtained is subjected to astage of chlorine/fluorine exchange in an anhydrous hydrofluoric acidmedium.

Two alternative forms have to date been explored in releasing the aminefrom the carbamoyl fluoride obtained after the exchange; these twoalternative forms are: the release of the amine by means of heating inthe presence of a large excess of hydrofluoric acid to givefluorophosgene or alternatively hydrolysis in a hydrofluoric acid mediumby a relatively small amount of water.

The technique using the decomposition of carbamoyl fluorides tofluorophosgene has the undoubted disadvantage of resulting in theconcomitant release of fluorophosgene, the toxicity of which is muchgreater than that of phosgene proper, which was used as a poison gasduring the First World War.

Another disadvantage of this technique is the increased consumption ofhydrofluoric acid, which is a relatively expensive reactant since it hasto be used in large excess.

The other techniques described, namely techniques using the in situhydrolysis of the carbamoyl fluoride, give yields which are far frombeing excellent.

These low yields put a serious strain on the cost price of the finalproduct and thus on the profitability of the complete operation.

Furthermore, the use of very large excesses of hydrofluoric acidinvolves subsequent recovery for economic reasons or for environmentalreasons, when the industrial plant is situated inland, which recoverycan be in particular:

either a recycling, as less costly, and a subsequent dehydration, whichrenders the recovery extremely disadvantageous as regards the cost priceof the operation;

or a neutralization, followed by a recovery in value of the salts thusobtained.

Finally, during the study which led to the present invention, it wasshown that, even when the aromatic ring of the molecule is depleted inelectrons, the reactivity of the carbamoyl fluorides is very high andresults in multiple byproducts which are injurious to the conversionyield, that is to say to the selectivity of the conversion. One of thepossible routes remaining open which allows easy access to the anilineis the return to the isocyanate. Thus, during the study which led to thepresent invention, it was shown that it is possible to proceed from thecarbamoyl fluoride to the fluorinated isocyanate, provided thatparticularly strict procedures are adhered to.

This part of the study has formed the subject matter of an internationalpatent application filed in France under the number PCT/FR00/01912 underpriority of the French application filed under the number 9908647. Theseapplications are published.

This technique, although it represented a significant advance, stillinvolved the recycling of large amounts of hydrofluoric acid. This iswhy the study was continued to examine whether it was possible to usethe discovery according to which the carbamoyl fluoride was not thesource of a large number of byproducts when it was in the presence of asignificant amount of isocyanate functional groups.

This is why one of the aims of the present invention is to provide afluorinating process which does not require a large excess ofhydrofluoric acid. Another aim of the present invention is to provide aprocess which makes it possible to achieve high conversion yields andhigh reaction yields.

Another aim of the present invention is to provide a process of thepreceding type which makes it possible to avoid the release, or at leastto limit the release, of fluorophosgene.

These aims, and others which will become apparent subsequently, areachieved by means of a process for the treatment of a derivativecarrying a perhalogenated carbon, advantageously in the benzyl or allylposition or carried by an atom exhibiting a free doublet, advantageouslya chalcogen, by means of a carbamoyl fluoride, advantageously anaromatic carbamoyl fluoride (that is to say, the nitrogen atom of whichis connected to an aromatic ring), characterized in that said derivativecarrying a perhalogenated carbon and said carbamoyl fluoride aresubjected to a temperature at least equal to 70° C., advantageously atleast equal to 90° C., and in that, at said temperature of at least 70°C., the ratio Q of; on the one hand, the sum of the hydrofluoric acid(HF) and of the carbamoyl fluorides to, on the other hand, the sum ofthe exchangeable halogens, of the isocyanate functional groups and ofthe carbamoyl fluorides is maintained, throughout the duration of thereaction, at a value at most equal to 1.2, advantageously to 1; indeedeven 0.9 in the final third of the final exchange.

The above ratio Q can be expressed as written below:$\frac{{HF} + \text{carbamoyl~~fluoride (s)}}{\text{exchangeable~~halogens} + \text{isocyanate} + \text{carbamoyl~~fluorides}}$

This ratio is targeted at all the entities present in the reactor,whether they are in the gas phase or whether they are in (the) liquidphase(s). If, in the case where the operation is being carried out in anopen (unclosed) reactor, the amount of HF in the gas phase cannot beeasily determined, only the HF in the liquid phase or phases will betaken into account.

All the halogens heavier than fluorine carried by the halophoric carbonor carbons are regarded as exchangeable [exchangeable halogens are thosewhich can be exchanged by the action of liquid hydrofluoric acid inlarge excess (more than 4 times stoichiometry) under autogenous pressureat a temperature of 100° C. for 10 hours].

The values indicated above are values which are expressed as equivalentsor, when the functional groups are monofunctional, as moles (ofsubstrate molecule).

The minimum overall value for the complete reaction, and thus theoptimum value from the economic viewpoint, is when the ratio Qapproaches the ratio:$\frac{\text{exchangeable~~halogens}}{\text{exchangeable~~halogens} + \text{isocyanate}}$

This minimum value has to be observed when all the reactants areintroduced at the beginning of the reaction.

However, according to the present invention, it is possible and evendesirable to gradually introduce the reactants, in particular thehydrofluoric acid, to move at the beginning of the reaction from time totime to much lower values.

The invention is targeted in particular at light substrates with acarbon number of at most 50, advantageously of at most 30, preferably ofat most 20 carbon atoms.

Thus, according to the present invention, it has been shown that it ispossible to use the fluoride of carbamoyl fluoride(s) as fluorine sourcemaking it possible to exchange a chlorine with a fluorine.

It has thus been possible to demonstrate that this technique, providedthat certain constraints are observed, makes it possible to avoid theformation of an excessively large amount of byproducts.

Under the conditions under which the invention is carried out, there isan equilibrium between the isocyanate, the carbamoyl fluoride and thedissolved HF (but the latter is in equilibrium with the gaseous form).This is the reason why it is difficult to distinguish the portion ofhydrofluoric acid in the reaction mixture. This is the reason why theratio is indicated in the form of a sum ratio.

The reaction is advantageously carried out in the presence of solventbut this is not necessary and, in particular, it is possible to use anexcess of isocyanate(s) as a solvent. This is particularly true when theisocyanate is too depleted in electrons to give rise to Friedel-Craftsreactions.

It is thus preferable for the aromatic entities to exhibit, in themedium, only rings depleted in electrons. The more depleted the rings,the less likely they are to give rise to side reactions. By way ofindication, it is thus desirable, for any benzene ring present, for thesum of the σ_(p) Hammett constants to be at least equal to 0.2;advantageously to 0.4; preferably to 0.7.

According to the present invention, not all the exchange necessarilytakes place at high temperatures (at least equal to 70° C.); only thepart of the reaction where the ratio Q′ is less than 0.8, preferablythan 1, should advantageously take place at these high temperatures.

Q′ is the ratio:$\frac{{HF} + \text{carbamoyl~~fluoride (s)}}{\text{isocyanate} + \text{carbamoyl~~fluoride(s)}}$

Although it is possible to operate at relatively high temperatures, itis preferable for the reaction to take place at temperatures at mostequal to 170° C., advantageously to 150° C., in particular in order forthe solubility of the hydrofluoric acid in the medium not to beexcessively low. This absence of solubility would result in excessivelyslow kinetics.

In order to prevent the boiling of the solvent from entraining gaseoushydrofluoric acid, it is preferable to choose solvents with a relativelyhigh boiling point in order for this boiling point, under the operatingconditions, to be greater than the working temperature. It isappropriate to choose solvents with a boiling point (starting boilingpoint in the case of a mixture) at atmospheric pressure of at least 100°C., advantageously of at least 120° C.

It is also advisable to choose the solvents so that they can be easilyseparated from the substrate and from the final product delivered.

The solvents which give good results are often those which are at leastpartially miscible with hydrofluoric acid and in particular fromhalogenated aromatic derivatives which do not react with the carbamoylfluoride. When the solvents are aromatic solvents, it is desirable fortheir ring(s) to be deactivated in order to avoid side reactions betweenthe starting substrate and the solvent, this being the case inparticular when, according to one of the embodiments of the invention, acatalyst based on Lewis acid is used. The active constituent of thecatalyst is chosen from Lewis acids and mixtures of Lewis acids.Generally, only a single Lewis acid is used.

The present invention is advantageous in particular when the carbamoylfluoride used as fluorinating agent is formed from the startingsubstrate, which then comprises both an isocyanate functional group anda functional group carrying halogen atoms to be exchanged with fluorine.Under these conditions, it is more practical to form the carbamoylfluoride or fluorides which will be used in the halogenation, morespecifically in the fluorination by exchange of halogen in situ; that isto say that the introduction is carried out into the medium comprisingthe isocyanates, initial, formed as reaction intermediate or formed asfinal product obtained by addition of gaseous hydrofluoric acid.

This is particularly advantageous in the case where the isocyanates arearomatic isocyanates, that is to say isocyanates connected directly toan aromatic ring.

In order for the reaction to be easy to implement, it is preferable forthere to be activation of the carbon carrying the heavier halogens thanfluorine to be exchanged with the latter. This activation is generallydue to conjugation with a pair of electrons can thus be due:

either to an unsaturation,

or to the presence of an atom carrying a doublet, itself optionallybonded to an unsaturation.

This can be expressed by indicating that the substrate comprises ahalophoric carbon of sp³ hybridization carrying at least two halogens,at least one of which is a halogen with an atomic number greater thanthat of fluorine, which halophoric carbon is connected to at least oneatom of low hybridization carrying an unsaturation or connected to anatom carrying a doublet capable of activating said halophoric carbonunder the operating conditions of the process.

Said atoms carrying doublets are advantageously chalcogens. The effectof the chalcogen increases in proportion as its rank increases; thus,sulfur is a more effective chalcogen than oxygen from the viewpoint ofthe activation of the halophoric carbon.

The halophoric carbon advantageously corresponds to the formula—CX₁X₂—EWG, where X₁ and X₂ represent alike or different halogens andthe EWG radical represents a halogen or group which represents ahydrocarbonaceous group, advantageously an electron-withdrawing group X₃(σ_(p) Hammett constant greater than 0); with the condition that atleast one, advantageously two, of the X₁, X₂ and EWG groups are halogensother than fluorine; the hyphen indicating the free bond connecting thehalophoric carbon to the X₁, X₂ and X₃ radical activating it beingdefined subsequently. Apart from the case where said atom of lowhybridization carrying an unsaturation participates in a carbon-carbonbond (acetylenic bond, preferably ethylenic bond, which ethylenic bonditself advantageously participates in a ring with an aromatic nature),it may be indicated, by way of teaching, by the example that,advantageously, said atom of low hybridization carrying an unsaturationis an atom which participates in one of the following double bonds[where *C is the halophoric carbon]:

Degree of aptitude Atom of low for the exchange the hybridizationreaction (easy = 1; and less easy = 2 but unsaturation more selective;which it relatively carries difficult = 3) Comments —*C—CR″═NR′ 2 WithHF already constitutes a base HF medium [the sequence can even be foundin substituted pyridines]* —*C—CR″═S′ 1 —*C—C═N—NH—R′ 2 With HF alreadyconstitutes a base HF medium* —*C—CR″═N—O—R′ 2 With HF alreadyconstitutes a base HF medium* —*C—CR″═PR′ 2 With HF already constitutesa base HF medium* —*C—N═NR′ 2 Compounds sometimes unstable, whichrestricts the range of the acceptable operating conditions —*C—CF═CF₂ 2—*C—N═O 2 May give rise to very complex mixtures —*C—NO₂ 3 To beavoided, may give rise to very complex mixtures

The reaction proceeds better in proportion as the halophoric carbon atomincreases in activity. The best activations are due either to thepresence of a double bond between the carbon and the sulfur, as isindicated in the preceding table, or, preferably, by the presence of achalcogen and/or of a phenyl ring, as is indicated later in thedescription.

To avoid side reactions, it is preferable to limit the potential amountof carbamoyl fluoride present in the reaction medium. This constraint isexpressed by the fact that the molar ratio of the hydrofluoric acid andthe carbamoyl fluoride, on the one hand, to the isocyanate and thecarbamoyl fluoride, on the other hand, [(HF+carbamoylfluoride)/(isocyanate+carbamoyl fluoride)] is at most equal to 1.5;advantageously to 1.2; preferably to 1; more preferably to 0.8; but itis preferable to carry out the addition of the hydrofluoric acid or ofthe carbamoyl fluoride gradually to a heel of solvent and of saidderivative brought to the chosen reaction temperature, the presence ofsolvent moreover being optional.

Under these conditions, it is possible to carry out the reaction withmore stringent constraints, namely that the addition is carried out at arate such that, in the final 90% of the reaction duration situated below100° C., advantageously below 90° C., the ratio of the hydrofluoric acidand the carbamoyl fluoride, on the one hand, to the isocyanate and thecarbamoyl fluoride, on the other hand, [(HF+carbamoylfluoride)/(isocyanate+carbamoyl fluoride)] is always at most equal to0.5; advantageously to 0.3; preferably to 0.1.

The reaction becomes correspondingly easier as the proportion offluorine among the halogens carried by the aliphatic halophoric carbon,that is to say of sp³ hybridization, decreases and it becomescorrespondingly easier as the proportion of isocyanate in the reactionmixture increases.

The reaction which is a subject matter of this communication can be usedeither to carry out selective exchange, leaving the final halogenheavier than fluorine on the halophoric carbon, or in particular tocarry out complete exchange, the excess hydrofluoric acid being limited.

Thus, according to an advantageous form of the present invention, inparticular when there are several exchanges to be carried out, thereaction can be carried out in several stages or in several steps. In afirst stage, the first exchange or exchanges. (one or two exchanges) arecarried out under cold conditions, that is to say at a temperature below60° C., advantageously below 50° C., preferably below 40° C., morepreferably below 30° C., and, in a second stage, the complete exchangeis obtained by heating at a temperature at least equal to 70° C.,advantageously to 90° C. The reaction can be easily carried outcontinuously in a cascade of reactors, the temperatures of whichcorrespond to the above conditions, cocurrentwise or countercurrentwise.The use of a plug flow reactor can be envisaged.

It is in particular in this second step that the presence of a catalystof Lewis acid type can be of use. The catalyst can be present in a(catalyst/substrate) molar ratio of 1% to 20%. If the catalyst ispresent throughout the exchange, it is preferable to limit its presenceto a molar ratio value at most equal to 0.1; indeed even at most to 5%;advantageously from 0.5 to 5%; preferably from 1 to 3%. If the use ofthe catalyst is restricted to the part of the process greater than 70°C., or to the final heavy halogen of the halophoric carbon, which can bedenoted by “final exchange”, it is possible to be placed in the top partof the range, that is to say at a presence in a molar ration of 1 to20%.

If the catalyst or catalysts are introduced into the mixture in the formof heavy halides, for the calculation of the ratio specified above, itwill be considered, before the calculation, that all the heavy halidesof the catalyst have been displaced by the fluoride of the hydrofluoricacid, the part of the hydrofluoric acid which has been used to displacesaid heavy halides from the catalyst no longer being available for theexchange. It is the same for the salts for which the acid associatedwith the anion is volatile under the operating conditions.

The most useful catalysts are antimony(V), tin(IV), tantalum andtitanium(IV) salts. Antimony and in particular tin are preferred.Titanium also makes possible excellent results. These salts can be usedalone or as mixtures. Generally, as the most practical, the salts of asingle element are used as catalyst.

As was said above, but expressed in a different manner, the reactionbecomes increasingly advantageous as the substrate and the carbamoylfluoride belong to the same line of reaction intermediates. This can beexpressed by indicating that said carbamoyl fluoride comprises analiphatic carbon, that is to say of sp³ hybridization, carrying at leasttwo halogens, advantageously at least one, preferably two, of which arefluorine. As was said above, said aliphatic carbon carrying one or morefluorines is advantageously a benzyl carbon, that is to say that it isattached directly to an aromatic ring, this said aromatic ringadvantageously being that which carries the nitrogen of the carbamoylfunctional group; in other words, when a compound comprises two aromaticrings, it is preferable for the halophoric carbon atom to be carried bythe same aromatic ring as that which carries the nitrogen of thecarbamoyl functional group or of the isocyanate functional group.

That which has just been said above can be expressed by indicating thatthe carbamoyl fluoride carrying the halogen atoms to be exchangedadvantageously corresponds to the following formula:

(R)_(m)—Ar(—Z—(CX₂)_(p)—EWG)—NH—CO—F

where:

Ar is an aromatic ring, advantageously with six ring members, preferablya homocyclic ring;

the X groups, which are alike or different, represent a fluorine or aradical of formula C_(n)F_(2n+1) with n an integer at most equal to 5,preferably to 2;

p represents an integer at most equal to 2;

EWG represents a hydrocarbonaceous group or an electron-withdrawinggroup, the possible functional groups of which are inert under theconditions of the reaction, advantageously fluorine or a perfluorinatedresidue of formula C_(n)F_(2n+1) with an integer at most equal to 8,advantageously to 5; the total number of carbons of —(CX₂)_(p)—EWG isadvantageously between 1 and 15, preferably between 1 and 10;

m is 0 or an integer chosen within the closed range (that is to say,comprising the limits) from 1 to 4; advantageously, m is at most equalto 2;

R is a substituent which is inert under the operating conditionsadvantageously chosen from halogens, advantageously light halogens (thatis to say, chlorine and fluorine), and hydrocarbonaceous radicals,preferably alkyl, aryl, alkylchalcogenyl (such as alkyloxyl) andarylchalcogenyl (such as aryloxyl) radicals;

Z represents a single bond or a chalcogen atom, advantageously a lightchalcogen atom (sulfur and oxygen).

Ar is advantageously monocyclic, preferably with six ring members.

The substrate corresponds more preferably to the formula below:

where:

Z represents a single bond or a chalcogen atom;

X₁ and X₂ represent alike or different halogens, with the condition thatat least one, advantageously both, halogens are other than fluorine;

R₁ and R₂ are substituents from halogens, alkyls, aryls or nitrites;

the X₃ radical is a halogen or electron-withdrawing group (σ_(p)constant greater than 0) which does not interfere with the reaction andin particular can be a perfluorinated group, generally denoted in thearea of technology by “R_(f)”;

with the condition that at least one, advantageously two, of the X₁, X₂and X₃ groups are halogens other than fluorine.

When the choice is made to use solvents, mention may be made, amongsolvents which give satisfactory results, of chlorobenzenes, inparticular monochloro-, dichloro- or trichlorobenzene, and theirmixtures.

The reaction is advantageously only halted when there remains at mostonly one halogen atom to be exchanged out of 100 initially present,preferably when there remains no more than 1% of molecules carrying atleast one halogen atom to be exchanged.

The following nonlimiting examples illustrate the invention.

Principles of the Reaction Tested

Development of a process which makes possible the preparation ofpara-(trifluoromethyl)benzene isocyanate (pTFMI) frompara-(trichloromethyl)benzene isocyanate (pTCMI) by reaction ofhydrofluoric acid according to the following diagram:

Although it does not appear here, the first reaction is the addition ofthe hydrofluoric acid to the isocyanate to form the carbamoyl fluoride.

EXAMPLE 1

Charge

chlorobenzene: 90.2 g

HF=31.5 g (3.86/pTCMI)

pTCMI: 97.2 g (0.407 mol)

The chlorobenzene is charged and then the autoclave is closed and cooledto 0° C. The HF is introduced at 0° C. with stirring. The autoclave isequipped with a weir which makes it possible to adjust the pressure. Thepressure is adjusted to ⅔ bar, the reaction medium is heated to 10° C.,the pTCMI is then introduced over approximately 10 minutes and thereaction medium is then heated at 25° C. under 2.5 bar for 7 h. Thereactor is degassed at 25° C. (weir opening) and is then cooled to 0° C.and left overnight.

The reaction medium is heated at 120° C. under autogenous pressure for 6h (pressure at the end of the test 9.4 bar). The analyses are carriedout by gas chromatography (GC).

Results: at the end of the fluorination at 25° C.

carbamoyl fluoride/isocyanate proportion=24/1

Distribution of the compounds as % area of the peaks of thechromatogram:

CF₃ compounds: 11%

CF₂Cl compounds: 71.5%

CFCl₂ compounds: 9.8%

CCl₃ compounds: 2%

Results: at the end of the treatment at 120° C.

carbamoyl fluoride/isocyanate proportion=77/21

Distribution of the compounds as % area of the peaks of thechromatogram:

CF₃ compounds: 79%

CF₂Cl compounds: 20%

CFCl₂ compounds: 0.5%

CCl₃ compounds: 0%

Estimation of the yield: sum of the organic compounds quantitativelydetermined: 67%

EXAMPLE 2

Charge

chlorobenzene: 90.2 g

HF=32 g (3.88/pTCMI)

pTCMI: 98.4 g (0.412 mol)

SbCl₅: 9.38 g (9.9 mol %)

The chlorobenzene and the SbCl₅ are charged and then the autoclave isclosed and cooled to 0° C. The HF is introduced at 0° C. with stirring.The autoclave is equipped with a weir which makes it possible to adjustthe pressure. The pressure is adjusted to ⅔ bar, the pTCMI is thenintroduced over approximately 10 minutes and the reaction medium is thenheated at 25° C. for 7 h. The reactor is degassed at 25° C. (weiropening) and then cooled to 0° C. and left overnight.

The reaction medium is heated at 120° C. under autogenous pressure for 6h.

Results: at the end of the fluorination at 25° C.

carbamoyl fluoride/isocyanate proportion=16

Distribution of the compounds as % area of the peaks of thechromatogram:

CF₃ compounds: 19.5%

CF₂Cl compounds: 68.1%

CFCl₂ compounds: 8.5%

CCl₃ compounds: 2.7%

Results: at the end of the treatment at 120° C.

carbamoyl fluoride/isocyanate proportion=1.5

Distribution of the compounds as % area of the peaks of thechromatogram:

CF₃ compounds: 84.3%

CF₂Cl compounds: 14.4%

CFCl₂ compounds: 0.4%

CCl₃ compounds: 0%

Estimation of the yield: sum of the organic compounds quantitativelydetermined: 86%

EXAMPLE 3

Charge

chlorobenzene: 90.3 g

HF=34.8 g (4.36/pTCMI)

pTCMI: 95.3 g (0.399 mol)

SbCl₅: 8.97 g (9.4 mol %)

The chlorobenzene and the SbCl₅ are charged and then the autoclave isclosed and cooled to 0° C. The HF is introduced at 0° C. with stirring.The autoclave is equipped with a weir which makes it possible to adjustthe pressure. The pressure is adjusted to 22 bar, the pTCMI is thenintroduced over approximately 10 minutes and the reaction medium is thenheated at 120° C. for 5 h.

Results: at the end of the fluorination treatment at 120° C.

carbamoyl fluoride/isocyanate proportion=4.2

Distribution of the compounds as % area of the peaks of thechromatogram:

CF₃ compounds: 90.5%

CF₂C1 compounds: 0.6%

CFCl₂ compounds: 0%

CCl₃ compounds: 0%

Estimation of the yield: sum of the organic compounds quantitativelydetermined: 85%

EXAMPLES 4 TO 10

Role of the Catalyst

They are carried out according to the same procedure:

solvent/pTCMI/catalyst are introduced into the autoclave:

the mixture is heated at T1

HF is introduced over X hours (per ⅔ g) and the pressure is adjusted to2 bar (final 2 h at T=T1)

the mixture is brought to atmospheric pressure

the mixture is heated at T2

final 2 h at T=T2

the reaction mass is cooled and the residual HF is removed by spargingwith nitrogen

the reaction mass is diluted with methylene chloride and then quicklywashed with water

the analysis is carried out on the solution in methylene chloride.

Operating conditions pTCMI (g) HF equiv. Solvent Mass solv. SbCl₅ equiv.T1 ° C. T2 ° C. X in hours 4 95.3 3.25 TCB 260.8 10% 60 120 2 5 95.863.2 TCB 102.6 10% 30 120 2 6 95.8 3.17 TCB 102.6 1.5%  60 120 2 7 94.83.22 TFMB 91.55 10% 60 120 2 8 96.37 3.85 TCB 102.6 10% 60 120 2 9 95.733.2 TCB 102 10% 60 120 2 10  96.2 3.1 CB 90.5 10   60 120 0.5 TFMB:trifluoromethylbenzene TCB: trichlorobenzene

Analytical Results

Analysis by GC. The carbamoyl fluoride of the pTFMI and the pTFMI arenot separated. The final product is composed very largely of pTFMI.

% pTcMI % pFDCMI % pDFCMI % pTFMI 4 0 72 5 0 73.3 6 2.5 0.8 2.8 80.7 7 00 0 71 8 0 0 0 73.2 9 0 0 0 73 10 1.5 0.6 2 66

EXAMPLES 11 TO 13

Influence of the Nature of the Catalyst and of the Final Temperature

Examples 11 to 13 are carried out according to the same procedure:

solvent/pTCMI/catalyst are introduced into the autoclave:

the mixture is heated at T1

HF is introduced over 2 h (per ⅔ g) and the pressure is adjusted to 2bar (final 2 h at T=T1)

the mixture is brought to atmospheric pressure

the mixture is heated at T2

final X hours at T=T2

the reaction mass is cooled and the residual HF is removed by spargingwith nitrogen

the reaction mass is diluted with methylene chloride and then quicklywashed with water

the analysis is carried out on the solution in methylene chloride.

Operating conditions pTCMI HF equiv. Mass solv. Cata. equiv. T sts (g)(mol) Solvent (g) Cata. (mol) T1 ° C. T2 ° C. X in hours 11 96 3.8Chloro- 76.7 SnCl₄ 3.2 60 120 2 benzene 12 95.9 3.65 TCB* 102.6 TiCl₄3.6 60 120 2 13 95.5 3.7 Chloro- 76.4 SnCl₄ 3.1 60 140 1 benzene *TCB:1,2,4-trichlorobenzene

Analytical Results

The yield is determined by GC analysis (the carbamoyl fluoride of thepTFMI and the pTFMI are not separated).

The pTFMI/carbamoyl fluoride of the pTFMI composition is determined byinfrared analysis.

Yd: pTFMI + carbamoyl % % Carbamoyl fluoride fluoride of the pTFMI pTFMIof the PTFMI 11 98.7 72 28 12 89.8 89 11 13 96.4 97 3

What is claimed is:
 1. A process for the treatment of a mixturecomprising a derivative of the formula:

wherein: Z represents a single bond or a chalcogen atom, wherein X₁, X₂and X₃ identical or different represent halogens, with the conditionthat at least two halogens are other than fluorine and are exchageableby the action of liquid hydrofluoric acid; R₁ and R₂ are halogens,alkyls, aryls or nitriles and X₃ is an electron-withdrawing group whichdoes not interfere with the reaction; and a carbamoyl fluoride, whereinsaid derivative and said carbamoyl fluoride are subjected to a reactiontemperature at least equal to 70° C. in the presence of hydrofluoricacid, and, wherein, at said temperature, the ratio of, on the one hand,the sum of the hydrofluoric acid (HF) and of the carbamoyl fluoride to,on the other hand, the sum of the exchangeable halogens, of theisocyanate functional groups and of the carbamoyl fluoride[(HF+carbamoyl fluoride)/(exchangeable halogen+isocyanate+carbamoylfluoride)] is maintained at a value at most equal to 1.2.
 2. A processaccording to claim 1, wherein the carbamoyl fluoride is an aromaticcarbamoyl fluoride, wherein said reaction temperature is at least equalto 90° C., further in the presence of a solvent, and wherein, the ratio[(HF+carbamoyl fluoride)/(exchangeable halogen+isocyanate+carbamoylfluoride)] is maintained at a value at most equal to
 1. 3. The processas claimed in claim 1, wherein said reaction temperature is at mostequal to 150° C.
 4. The process as claimed in claim 2, wherein saidsolvent exhibits a boiling point of at least 100° C.
 5. The process asclaimed in claim 2, wherein the solvent is miscible with hydrofluoricacid, and is a halogenated aromatic derivative which does not react withthe carbamoyl fluoride.
 6. The process as claimed in claim 2, whereinsaid carbamoyl fluoride is added into the mixture between the solventand the derivative or is formed in situ by addition of anhydroushydrofluoric acid into the mixture.
 7. The process as claimed in claim1, wherein the molar ratio [(HF+carbamoylfluoride)/(isocyanate+carbamoyl fluoride)] is at most equal to 0.8. 8.The process as claimed in claim 6, wherein the addition of the carbamoylfluoride or of the hydrofluoric acid, in the form of a solution, takesplace gradually to a heel of solvent and of said derivative brought tothe reaction temperature.
 9. The process as claimed in claim 8, whereinthe addition is carried out at a rate such that, in the final 90% of thereaction time situated below 90° C., and the ratio [(HF+carbamoylfluoride)/(isocyanate+carbamoyl fluoride)] is always at most equal to0.1.
 10. The process as claimed in claim 1, wherein said carbamoylfluoride comprises an aliphatic carbon carrying at least two halogens,including at least two fluorines.
 11. The process as claimed in claim10, wherein said aliphatic carbon carrying at least two fluorines is abenzyl carbon directly attached to an aromatic ring.
 12. The process asclaimed in claim 11, wherein said aromatic ring is that carrying thenitrogen of the carbamoyl functional group.
 13. The process as claimedin claim 1, wherein said carbamoyl fluoride corresponds to the formula:(R)_(m)—Ar(—Z—(CX₂)_(p)—EWG)—NH—CO—F wherein: Ar is an homocyclicaromatic ring; the X groups, which are identical or different, representa fluorine or a radical of formula C_(n)F_(2n+1) with n an integer atmost equal to 5; p represents an integer at most equal to 2; EWGrepresents a hydrocarbonaceous group, an electron-withdrawing group,optionally having functional groups which are inert under the conditionsof the reaction, or a perfluorinated residue of formula C_(n)F_(2n+1)with n being an integer at most equal to 8; the total number of carbonsof —(CX₂)_(p)—EWG is between 1 and 15; m is 0 or an integer chosenwithin the closed range from 1 to 4; R is a substituent which is inertunder the operating; and Z represents a single bond or a chalcogen atom.14. The process as claimed in claim 2, wherein the solvent is amonochlorobenzene, dichlorobenzene or trichlorobenzene.
 15. The processas claimed in claim 1, wherein the mixture further comprises a catalystwhose active constituent is a Lewis acid.
 16. The process as claimed inclaim 15, wherein said catalyst is only added into the mixture when thelatter reaches a temperature of 70° C.
 17. The process as claimed inclaim 15, wherein said catalyst is only added into the mixture when thesubstrate has, statistically, no more than a single halogen to beexchanged with the fluorine.
 18. The process as claimed in claim 15,wherein said catalyst comprises an antimony(V) salt.
 19. The process asclaimed in claim 15, wherein said catalyst comprises a tin(IV) salt. 20.The process as claimed in claim 15, wherein said catalyst comprises atitanium(IV) salt.
 21. The process as claimed in claim 15, wherein saidcatalyst is in the form of a halide or of a mixture of halides.